A Pragmatic Trial With Optimized Dose of Rifampicin and Moxifloxacin for the Treatment of Drug Susceptible Pulmonary Tuberculosis
Tuberculosis (TB) remains a major global public health problem, particularly in low- and middle-income countries (LMICs) in Africa, Asia, and Eastern Europe. Approximately 10 million people fall sick with TB, causing up to 2 million deaths, worldwide per year. Considerable progress was made in TB control from 1990-2015, motivating the World Health Organization (WHO) to launch an ambitious EndTB strategy. However, the effect of the ongoing Coronavirus Disease 2019 (Covid-19) pandemic has been devastating and the last two years have seen the first year-on-year increases (of 5.6%) in TB mortality since 2005 . In order to regain lost ground, and re-establish progress towards elimination of TB, innovation is needed in all aspects of TB control, including development of shorter treatment regimens for drug susceptible (DS) and multi-drug resistant / rifampicin resistant (MDR/RR) forms of the disease. This protocol seeks to conduct the TB clinical trial combining the 8-methoxyfluroquinolone and optimised dose of rifamycing to address two questions. The first is to confirm the non-inferiority of a four-month optimised dose rifamycin and moxifloxacin-based regimen amongst African TB patient populations with high rates of co-incident HIV. Secondly, we seek to establish that the rifamycin of choice in potent 4-month anti-TB treatments could be rifampicin as this will be more rapidly up-scalable for public health impact.
• Each patient must meet all the following inclusion criteria prior to enrolment into the trial:
‣ The patient has given fully informed, signed written or witnessed oral informed consent for study participation prior to all trial-related procedures, including HIV testing if HIV status is not known.
⁃ The patient has a diagnosis of pulmonary TB established by Xpert MTB/RIF® result which confirms low medium or high level detection of M tuberculosis and does not detect rifampicin resistance.
• If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at the trial laboratory, and the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
∙ If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at a non-trial laboratory, but the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
∙ If the patient has been referred to the study from a clinic from which the full pre-screening clinical diagnostic Xpert MTB/RIF® test result is unavailable, a repeat Xpert MTB/RIF® assay should be performed by the study laboratory to confirm eligibility before recruitment.
⁃ The patient should be aged ≥ 18 years on the day of providing informed consent.
⁃ The patient has a body weight in light clothing and without shoes of at least 35kg.
⁃ Female patients of child-bearing potential must have a negative urine or serum pregnancy test ≤ 7 days prior to screening, and consent to practice an effective method of contraception until completion of therapy.
⁃ The patient must have a verifiable residence location and telephone number that is accessible if necessary for contact during follow-up.